Process for preparing polyhalogenated carbinols

ABSTRACT

There is disclosed a process for preparing polyhalogenated carbinols having formula: ##STR1## by reacting a compound having formula: ##STR2## with a system consisting of a compound having formula: ##STR3## and of a divalent metal or of a metal salt, in protic dipolar solvents, in which formulae 
     R=H, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkadienyl, phenyl, naphthyl, anthracyl group, a heterocyclic radical, optionally substituted; 
     R&#39;=H, a haloalkyl, --CN, --COOR&#34; group with R&#34; equal to H or to an alkyl group; 
     X 1  =Cl, Br; =X 2  =F, Cl, Br; 
     X 3  =Cl, Br, CF 3 , CCl 3  ; Y=Br or Cl when X 1 , X 2  and X 3  are different from Br.

This is a Division of application Ser. No. 205,506 filed June 7, 1988which in turn is a continuation of application Ser. No. 071,540, filedJuly 7, 1987, which in turn is a continuation of application Ser. No.817,542, filed January 10, 1986, all now abandoned.

The present invention relates to a process for preparing polyhalogenatedcarbinols by reacting a carbonylic compound with a system consisting ofa polyhalogenated hydrocarbon and of a divalent metal or of a metal saltin aprotic dipolar solvents.

The polyhalogenated carbinols are important intermediate products infine chemistry and in particular in the field of pesticides for thepreparation, for instance, of benzoylureas and pyrethroides having aninsecticidal activity.

BACKGROUND OF THE INVENTION

The literature discloses the preparation of a few polyhalogenatedcarbinols, in particular the carbinols containing --CCl₃ or --CBr₃groups, using synthesis methods different from the present invention,such as, for instance, those described in: Journal of American ChemicalSociety, 1948, pages 1189 and 1950, pages 5012-14; Bulletin de laSociete Chimie de France, 1967, pages 1520-32; British patentapplication 2,076,804 and Japanese patent application 77/73.842.

THE PRESENT INVENTION

We have now found a simple and economical method for obtainingpolyhalogenated carbinols with good yields. Thus, the object of thisinvention is a process for preparing polyhalogenated carbinols havinggeneral formula: ##STR4## consisting in reacting a carbonylic compoundhaving formula: ##STR5## with a system consisting of a polyhalogenatedhydrocarbon having formula: ##STR6## and of a divalent metal or of ametal salt, in an aprotic dipolar solvent, at temperatures rangingbetween -20 and the boiling temperature of the solvent, wherein the saidformulas

R represents a H atom, an alkyl, cycloalkyl, alkenyl, cycloalkenyl,alkadienyl group, which groups may be substituted, preferably on thefirst two carbon atoms of the aliphatic chain, by one or more groupsselected among a halogen atom, aryl groups, --CN, --NO₂, --COOR" whereinR" is H or a C₁ -C₄ alkyl group, said R further represents a phenyl,naphthyl, anthracyl group, a heterocyclic radical, optionallysubstituted by one or more groups selected among halogen atoms, alkyl,alkenyl, alkoxyl, --NO₂, --CN, haloalkyl, haloalkenyl, haloalkoxy,thioalkyl, alkylamino, dialkylamino, --COOR" and --COR" groups;

R' represents H, a haloalkyl, --CN, --COOR" group;

X¹ represents Cl, Br;

X² represents F, Cl, Br;

X³ represents Cl, Br, CF₃, CCl₃ ;

Y represents Br or Cl when X¹, X² and X³ are different from Br.

As a metal use may be made, for instance, of: zinc, copper, iron,magnesium, and as metal salt, use may be made, for instance, of stannouschloride.

As solvent there can be used: dimethylformamide, dimethylsulfoxide,hexamethylphosphorotriamide, N-methylpyrrolidone, sulfolane,N,N-dimethyl-imidazolidinone.

The reactions, which take place successively during the process can berepresented schematically according to the following equations: ##STR7##wherein M represents the metal.

The operating conditions for the addition of the reactants in theprocess, according to the present invention, can vary according to thetype of compounds utilized and, in any case, said operating conditionsare not a critical factor.

An operating condition concerning the addition consists in adding themetal in only one solution or in subsequent shares to a mixtureconsisting of hydrocarbon III, of carbonylic compound II and of reactionsolvent. Alternatively, hydrocarbon III, optionally dissolved in thereaction solvent, can be added to a suspension of the metal in thereaction solvent, in the presence of carbonylic compound II.

Said operating conditions have to be recommended when the organometalliccompound having formula (III M), which forms during the reaction, turnsout not to be very stable and therefore tends to give rise toundesirable by-reactions. Should organometallic compound (III M) besufficiently stable, such as, for instance,1,1-dichloro-2,2,2-trifluoro-ethyl zinc chloride, it is possible to workaccording to another operating condition consisting in separatelypreparing compound (III, M), by heating the metal in a suitable solventwith a slight excess of hydrocarbon III till dissolution and then inmixing said compound with carbonylic compound II dissolved in thereaction solvent.

The process is carried out using the reactants in substantiallystoichiometric ratios. However, it would be preferable, according to thecharacteristics of the concerned reactants, to use an excess withrespect to the stoichiometric of both the metal with respect tocarbonylic compound II and of hydrocarbon III with respect to the metal.

The compounds of general formula I, wherein X³ represents CF₃ and thecompounds having general formulas ##STR8## wherein X¹, X², X³ and R"have the meaning as defined in formula (I); Q represents H, a halogenatom, a C₁ -C₃ alkyl group optionally substituted by 1-3 halogen atoms,--OCH₃, --SCH₃, --OCF₃ ; n is a whole number comprised between 1 and 4,are new compounds and form a further object of the present invention.

Furthermore, we have found that the carbinols having general formula (I)can be reduced to alkenes having general formula: ##STR9## using knownmethods such as, for instance: (a) direct treatment of carbinol (I) withzinc in acetic acid;

(b) conversion of carbinol (I) to acetate or to dihalophosphite andsubsequent treatment with zinc in dimethylformamide;

(c) substitution of the hydroxyl radical of carbinol (I) with a halogenatom and subsequent dehalogenation by means of zinc.

In the aforesaid conversions, it is generally possible to use carbinol(I) in the same reaction medium in which it has been prepared accordingto the present invention, namely without isolating it, with considerableeconomic advantages, as well as with advantages concerning thesimplicity of carrying out the process for obtaining the correspondingalkenes.

Alkenes of formula (IV) are, in their turn, important intermediatecompounds for the preparation of pesticides. In particular, carbinols offormula (IV) can be reduced, according to the aforesaid methods, toalkenes having formula: ##STR10## which, after reduction to thecorresponding anilines and reaction with suitable isocyanates, provideinsecticidal benzoylureas.

The carbinols of formula (V) can be reduced, according to the aforesaidmethods, to alkenes of formula: ##STR11## which are successivelyconverted to the respective acid chlorides and then esterified to giverise to pyrethroides, insecticides having a very high activity and alarge action spectrum.

The following examples are given to illustrate the invention in moredetail but are not intended to be limiting.

EXAMPLE 1 Preparation of 1-phenyl-2,2,2-trichloro-ethanol

A solution containing 3.18 g of benzaldehyde (30 millimoles), 6.16 g ofcarbon tetrachloride (40 millimoles) in 30 ml of DMF dehydrated onmolecular sieves was loaded into a small 3-neck flask having a capacityof 100 ml provided with a reflux cooler, thermometer, magnetic stirrerand kept under a nitrogen atmosphere.

720 mg (30 milligram atoms) of magnesium in the form of shavings wereadded in doses; in the beginning the mixture was heated to about 40° C.,then after the reaction had started, the metal addition and the thermalregulation were checked in order to keep the inner temperature at about50° C.

When magnesium was almost completely dissolved, the whole was heated at60° C. for 1 h and then at room temperature overnight.

The mass was then diluted with 250 ml of water, acidified withhydrochloric acid at 10%, extracted with 3 shares of ethyl ether, eachof them corresponding to a volume of 80 ml; the organic extract waswashed with 50 ml of a saturated solution of sodium chloride, dehydratedwith sodium sulphate and concentrated. The residue was analyzed bychromatography on a silica gel column, by eluting with hexane/ethylacetate in a 95:5 ratio. 3.2 g of the reaction product were obtained.

¹ H-NMR (CDCl₃,TMS), δ (ppm): 3.35 (1H, S); 5.13 (1H, S) 7.1-7.7 (5H,m).

IR (9 cm⁻¹): 3440 (--OH).

EXAMPLE 2 Preparation of 1-phenyl-2,2,2-tribromo-ethanol

2.12 g of benzoic aldehyde (20 millimoles), 25 ml of DMF, 6163 g ofcarbon tetrabromide (20 millimoles) were loaded into a small 3-nectflask having a capacity of 100 ml, provided with a reflux cooler,thermometer, magnetic stirrer, under nitrogen atmosphere.

1.3 g of zinc (20 milligram atoms) were added in small doses in order tokeep the temperature at about 45° C., after having finished theaddition, the whole was heated at 50° C. for 1 h. The mixture aftercooling was poured into 200 ml of water, acidified with HCl at 10%,extracted with 3 portions of ethyl ether each of them corresponding to avolume of 75 ml; the organic extract was washed with a solution ofsodium chloride, dehydrated and concentrated.

The product was purified by chromatography on silica gel, by elutingwith hexane/ethyl acetate having a 95:5 ratio. 3.3 g of a solid wereobtained having a m.p. of 73° C.

¹ H-NMR (CDCl₃, TMS), δ (ppm): 3.80 (1H, S); 5.18 (1H, S) 7.1-7.8 (5H,m).

EXAMPLE 3 Preparation of ethyl 2-hydroxy-2-tribromomethyl-propionate

3.31 g of carbon tetrabromide (10 millimoles), 1.16 g of ethyl piruvate(10 millimoles) and 10 ml of DMF were mixed under nitrogen atmosphere ina small flask having a capacity of 100 ml.

650 mg (10 milligram atoms) of zince in powder were added, in successiveportions, under stirring, the temperature of the reaction mixture beingkept at about 45° C.

The heating was continued at such temperatures for 2 h, then the masswas diluted with 120 ml of water and 30 ml of a saturated solution ofammonium chloride, extracted with 3 shares of ethyl ether, each of themhaving a volume of 50 ml, dehydrated with sodium and concentrated in arotary evaporator. The raw product of reaction was purified by columnchromatography by eluting with hexane/ethyl acetate having a 95:5 ratio.1.6 g of product were obtained.

¹ H-NMR (CDCl₃, TMS), δ (ppm): 1.35 (3H, t); 1.85 (3H, S) 4.35 (2H, q);4.45 (1H, S).

IR (cm⁻¹): 3460 (--OH); 1740 (--COOEt).

EXAMPLE 4 Preparation of ethyl2-(2,2-dichloro-1-hydroxy-3,3,3-trifluoropropyl)-3,3-dimethyl-cyclopropane-carboxylate

9.8 g of Zn in powder (0.15 gram atoms) and 37.5 g of1,1,1-trichloro-2,2,2-trifluoro-ethane (0.2 moles) in 125 ml ofanhydrous THF were reflux heated under nitrogen atmosphere until themetal was dissolved, after which solvent and freon in excess wereremoved by distillation at reduced pressure.

The residue was dissolved in 50 ml of DMF and 17 g (0.1 moles) of ethyl3,3-dimethyl-2-formyl-cyclopropanecarboxylate (cis-trans mixture)dissolved in 50 ml of DMF were added to said solution.

Always under nitrogen atmosphere and under stirring, the mass was heatedat 45° C. for 5 hours. After cooling it was diluted with 500 ml ofacidulated water and extracted with 3 shares of ethyl ether, each ofthem having a volume of 150 ml. The extract was washed with a solutionof sodium chloride (100 ml), then dehydrated and concentrated.

After separation by column chromatography (eluent hexane/ethyl acetate95:5) 19,5 g of carbinol (cis-trans mixture 45:55) were obtained.

¹ H-NMR (CDCl₃, TMS), δ (ppm): 1.1-1.4 (9H, m); 1.55-2.1 (2H, m); 2.7(1H, S); 3.75 (1H, d); 4.08 (2H, q).

EXAMPLE 5 Preparation of 2,2-dibromo-3,3,3-trifluoro-1-(2-chlorophenyl)propanol ##STR12##

83.5 g of CF₃ CBr₃ in anhydrous DMF and 28 g of 2-chlorobenzaldehydewere reacted under a nitrogen atmosphere. The mixture was brought to 5°C. and zinc in powder (g. 16.0) was added to it slowly. Then the mixturewas let reach the room temperature and kept under stirring for 6 hours.The mixture was poured into water and extracted three times with ethylether.

The ethereal extract was shaken with an aqueous solution of sodiumbisulfite in order to eliminate the non-reacted aldehyde, and then wasdehydrated with anhydrous sodium sulphate. After filtration, the residuewas concentrated under vacuum and purified by chromatography on silicagel, by eluting with hexane/ether 95:5. 30 g of product were thusobtained.

¹ H-NMR (δ, THS=0); 8.0-7.4 (m, 4H, Arom.); 6.9 (d, 1H, CH); 3.3 (sbroad, 1H, OH).

EXAMPLE 6 Preparation of 2,2-dichloro-3,3,3-trifluoo-1-phenyl propanol##STR13##

3 g of benzaldehyde and 5.3 g of CF₃ -CCL₃ were reacted in 30 ml ofanhydrous DMSO, under nitrogen atmosphere. 5.3 g of anhydrous SnCl₂ wereadded at room temperature and the mixture was kept at room temperatureunder stirring for 10 hours. Then the whole was poured into water andextracted with ether.

The ethereal solution was shaken with a solution of sodium bisulfite inorder to eliminate the non-reacted benzaldehyde and then dehydrated onanhydrous sodium sulphate. The ether was removed under vacuum and 4.4 gof product were obtained.

¹ HMNR (CDCl₃, TMS) δ (ppm); 2.9 (1H, S) OH; 5 (1H, S) CH; 7.2 (5H, m)aromatic.

EXAMPLE 7 Preparation of2,2-dichloro-3,3,3-trifluoro-1-(3-pyridyl-1-propanol) ##STR14##

5 g of 3-pyridine-carboxy-aldehyde in 100 ml of anhydrous DMF and 34 gof CF₃ CCl₂. ZnCl prepared previously were reacted under a nitrogenatmosphere. The mixture was heated at 40° C. for 4 h, then poured intowater and extracted with ether several times. The collected organicextract was dehydrated on anhydrous sodium sulphate and thenconcentrated under vacuum. 9 g of a white solid were obtained having amelting point of 141°-143° C.

EXAMPLE 8 Preparation of2,2-dichloro-3,3,3-trifluoro-1-(4-nitrophenyl)-propanol ##STR15##

0.066 moles of p-nitrobenzaldehyde and 0.080 moles of the complex Zn-CF₃CCl₃ prepared previously were reacted in 100 ml of anhydrous DMF under anitrogen atmosphere. The whole was heated at 35°-40° C. for 3 h, thenpoured into water, acidified with dilute HCl and extracted 3 times withethyl ether. The collected organic extract was brought to a neutral pHby washings with water and, after dehydration on anhydrous sodiumsulphate was concentrated under vacuum.

18 g of a clear solid were thus obtained, having a melting point of 102°C.

EXAMPLE 9 Preparation of2,2-dichloro-3,3,3-trifluoro-1-(2,6-dichloro-4-nitrophenyl)-1-propanol##STR16##

3 g of 2,6-dichloro-4-nitro benzaldehyde were reacted, in 20 ml ofanhydrous DMF under a nitrogen atmosphere, with CF₃ CCl₂ ZnCl preparedfrom 5 g of CF₃ CCl₃ and 2.2 g of Zn in 10 ml of THF at 60° C. for 1hour. The mixture was heated at 50° C. for 2 hours and at the end of thereaction it was poured into acidulated water and extracted repeatedlywith ethyl ether.

After having removed the ethyl ether under vacuum, 3.5 g of product wereobtained.

¹ H-NMR (CDCl₃, TMS) δ (ppm): 4.3 (1H, d); 6.35 (1Hd); 8.15 (2H, s).

EXAMPLES 10-24

By working under the operating conditions of the preceding examples, 15carbinols were prepared, the characteristics of which are reported inthe Table.

                                      TABLE                                       __________________________________________________________________________     ##STR17##                                                                    Ex.                                                                           No.                                                                              R             R'                                                                              X.sup.1                                                                         X.sup.2                                                                         X.sup.3                                                                          .sup.1 H-NMR (δ, TMS = O)                                                            Mass spectrum m.p.                     __________________________________________________________________________    10                                                                                ##STR18##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         --           m/e 223; 181; 156; 151; 101; 55                                               (base peak)                            11                                                                                ##STR19##    H Br                                                                              Br                                                                              Br --           m/e 279; 243; 73; 55 (base peak)                                              m.p. 54-55°                     12 CCl.sub.3     H Cl                                                                              Cl                                                                              CF.sub.3                                                                         --           m/e 263; 181 (base                                                            peak) 151; 147; 111                    13                                                                                ##STR20##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         7.6-6.8 (m, 3H); 5.4 (s broad, 1H); 3.9 (s                                    broad, 1H    m/e 264 (H.sup.t); 247; 212;                                                  113(base peak)                         14                                                                                ##STR21##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         7.1-6.7 (m, 3H, Arom) 5.2 (d, 1H, CH); 3.9 (s,                                6H, CH.sub.3); 3.2 (d, 1H, OH)                                                             m.p. 118-120° C.                15                                                                                ##STR22##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         10.9 (s, 1H, phenolic OH); 7.5-6.7 (m, 3H                                     Arom); 5.5 (s, 1H, CH 4.5 (broad, OH,                                                      --)                                    16                                                                                ##STR23##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         7.9-7.4 (m, 7H, Arom) 5.3 (s broad, 1H, CH);                                  3.7 (s broad, 1H, OH)                                                                      m.p. 56-58° C.                  17 OHCCH.sub.2   H Cl                                                                              Cl                                                                              CF.sub.3                                                                         --           m/e 206; 178; 171;                                                            151; 109; 45                                                                  (base peak)                            18                                                                                ##STR24##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         --           m/e 221; 156; 151;  99; 57 (base                                              peak)                                  19                                                                                ##STR25##    H Br                                                                              Br                                                                              CF.sub.3                                                                         4.1 (q, 2H, CH.sub.2); 3.7 (d, 1H, CHOH); 2.8                                 (s broad, 1H, OH); 2.1-1.6 (m, 2H); 1.4-1.2 (m,                               9H, CH.sub.3)                                                                              --                                     20                                                                                ##STR26##    H Br                                                                              F CF.sub.3                                                                         --           m/e 335; 305; 225; 179; 141            21                                                                                ##STR27##    H Br                                                                              Br                                                                              Br 4.1 (q, 2H, CH.sub.2); 3.7 (d, 1H, CHOH); 3.0                                 (s, broad, 1H, OH; 1.8-1.6 (m, 2H, CHCH;                                      1.4-1.2 (m, 9H, CH.sub.3)                                                                  --                                     22                                                                                ##STR28##    H Cl                                                                              Cl                                                                              Cl 10.6 (s, 1H, CHO); 8.1-7.4 (m, 4H, Arom); 5.3                                 (s, 1H, CH); 4.7 (broad 1H, OH)                                                            --                                     23                                                                                ##STR29##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         9.9 (s, 1H, CHO); 8.1-7.8 (q, 4H, Arom); 5.5                                  (s, 1H, CH); 3.8 (broad, 1H, OH)                                                           --                                     24                                                                                ##STR30##    H Cl                                                                              Cl                                                                              CF.sub.3                                                                         7.4 (t, 1H) + 6.4 (dd, 2H, Arom); 5.2 (d broad,                               1H, CH); 3.8 (d, broad, 1H, OH)                                                            --                                     __________________________________________________________________________

EXAMPLE 25 Preparation of ethyl2-(2-chloro-3,3,3-trifluoro-2-propenyl)-3,3-dimethyl-cyclopropanecarboxylate

1.6 g (5 millimoles) of ethyl2-(2,2-dichloro-1-hydroxy-3,3,3-trifluoro-propyl)-3,3-dimethyl-cyclopropanecarboxylate,prepared as described in Example 4, were dissolved in 10 ml of DMF and 5ml of pyridine; 1 ml of acetic anhydride was added to the mixture, thatwas kept at room temperature for 2 h under stirring.

When all the carbinol was converted into acetate (gaschromatographiccontrol), 520 mg (8 milligram atoms) of zinc in powder were added andthe mixture was heated at 60° C. for 2 h. The mixture was then treatedunder the usual conditions and the residue was purified chromatographyon silica gel. 1.2 g of the desired product were obtained.

¹ H-NMR (CDCl₃, TMS, (ppm): 1.1-1.4 (9H, m); 1.65-2.55 (2H, m); 4.1 (2H,q); 5.7-6.2 (1H, m).

EXAMPLE 26 Preparation of3,5-dichloro-4-(2-chloro-3,3,3-trifluoro-1-propenyl)-aniline(intermediate for insecticides) ##STR31##

3.5 g of2,2-dichloro-3,3,3-trifluoro-1-(2,6dichloro-4-nitrophenyl-1-propanol,prepared as described in Example 9, were dissolved in pyridine (15 ml)and treated with 1.5 g of acetic anhydride.

After 3 h the whole was poured into water and ice and then extracted 3times with ether using 70 ml at a time. The ethereal phase was washedwith N/10 HCl in order to eliminate the excess pyridine, and neutralizedwith sodium bicarbonate in a saturate solution. The ether was thenremoved thereby obtaining 3.4 g of acetate. 0.6 g of acetate weretreated with 0.95 g of iron in powder in 6 ml of ethanol and 1.5 ml ofH₂ O acidified with 0.05 ml of concentrated HCl. The mixture was heatedat 80° C. for 4 h, then poured into water, brought to pH 9 and extracted3 times with 50 ml of ethyl ether at a time.

After drying on sodium sulphate, 0.33 g of aniline were obtained.

¹ H-NMR (CDCl₃, TMS), δ (ppm); 3.9 (2H, broad); 6.6 (2H, s); 7.2 (1H,s).

EXAMPLE 27 Preparation of 2-chloro-3,3,3-trifluoro-1-phenyl-propene##STR32##

20 ml of DMF, 3500 g of benzaldehyde and 3,160 g of CF₃ CCl₃ were loadedinto a 50 l flask under a nitrogen atmosphere. The temperature wasbrought to -5° C., 2 g of bisublimed I₂ were added and then, in smallshares, over about 2 h, Zn (3,313 g) in powder previously activated inorder to restrain the reaction exothermicity. The temperature was letreach 15° C. and after 15 minutes 5 l of acetic anhydride were added tothe mixture. The temperature was brought to 55° C. and after 1 h afurther amount of Zn in powder (2,800 g) was added. The whole was heatedat 80° C. for 11/2 h, then cooled, and poured into H₂ O. The mass wasacidified with HCl and extracted at room temperature with 30 l of CH₂Cl₂ (twice).

The organic extract was washed till neutral pH and concentrated. Theresidue (6,920 g) was distilled at reduced pressure thereby obtaining5,185 g of prodcut (m.p. 61° C. at 4 mm Hg).

We claim:
 1. A polyhalogenated carbinol of the formula: ##STR33##